Researchers Identify Genes that Control Development of Fat Tissues

Harvard School of Public Health (HSPH) researchers have identified two genes that control the development of fat tissues in mice, providing a critical step in the potential ability to prevent and reverse obesity at genetic levels.

GATA-2, GATA-3 Fat Genes

Until now, no one knew the specific trigger that controls the extent to which cells called preadipocytes turn into fat cells. The researchers have identified the genes GATA-2 and GATA-3 as the molecular gatekeepers of that transition. When the genes are defective or missing, preadipocytes change into fat cells and, conversely, when the genes are expressed, preadipocytes remain fixed in a pre-fat stasis and do not accumulate lipids.

“If a gene is controlling this critical gate, then one can control the fat tissue in two ways,” said Gökhan Hotamisligil, associate professor in the Division of Biological Sciences and Department of Nutrition, who led the study. “Theoretically, one can enhance or diminish the formation of fat cells depending on how one manipulates the genes.”

Fat Cells in Flies

In their experiments, the researchers first examined genes that produce fat cells in flies and found analogous genes in mice and humans. Working with the mice genes, the researchers further identified GATA-2 and GATA-3 expressed in specialized “white” fat cells that are commonly found in adult humans.

Control Fat Cell Generation

They then demonstrated that through molecular manipulation of these genes it is possible to limit or encourage fat cell generation. The identification could also produce methods to convert white fat cells into so-called “brown” fat cells that burn off more easilyor to effectively reverse obesity.

Conversely, the research could lead to ways in which to stimulate white fat cells to add energy stores in the body for people struggling with dissipative diseases such as AIDS.